Stearoyl-CoA desaturase (SCD1) is a microsomal, enzyme that catalyzes the de novo biosynthesis of monounsaturated fatty acids from saturated fatty acyl-CoA substrates in mammals. Specifically, SCD1 introduces a cis-double bond in the C9-C10 position of saturated fatty acids such as palmitoyl-CoA (16:0) and stearolyl-CoA (18:0). The resulting monounsaturated fatty acids, palmitoleoyl-CoA (16:1) and oleoyl-CoA (18:1), are in turn substrates for incorporation into a variety of lipids, such as phospholipids, cholesterol esters, and triglycerides. Monounsaturated fatty acids are also mediators of several other processes such as signal transduction and cellular differentiation. Lipid composition is of considerable physiologic importance. As the key component of cellular membranes, phospholipid composition ultimately determines membrane fluidity, while the composition of cholesterol esters and triglycerides may impact lipoprotein metabolism and adiposity. Studies in mice further suggest that SCD1 activity is important to maintaining the normal functioning of the skin and eyelid as a result of its major role in lipid synthesis within sebaceous and meibomian glands. Miyazaki, J. Nutr., 131:2260-2268 (2001). SCD1 expression has been confirmed in the sebaceous glands of human scalp skin by immunohistochemistry and in the immortalized sebaceous gland cell line SZ95 by RT-PCR.
Skin is a lipid rich organ composed of three primary layers: the stratum corneum, the epidermis, and the dermis. The stratum corneum is the outer layer and its primary function is to serve as a barrier to the external environment. To decrease the stratum corneum's permeability to water and to keep the skin from cracking, sebaceous glands secrete an oily substance called sebum which is distributed onto the skin surface. Sebum is also secreted by the meibomian glands (or tarsal glands), a special kind of sebaceous gland located along the rim of the eyelids, to prevent evaporation of the eye's tear film. Sebum is a complex lipid mixture generally comprising free fatty acids, triglycerides, sterol esters, wax esters and squalene; however, its exact composition varies from species to species. Sebum is produced in the acinar cells of the sebaceous glands and accumulates as these cells age. Upon reaching maturation, the acinar cells lyse releasing sebum into the lumenal duct so that it may be deposited on the surface of the skin.
In humans, sebaceous glands are present in all areas of the skin except for the palms of the hands and soles of the feet. The highest concentration of these glands occurs on the scalp and face. Despite the important functions that sebum plays, many individuals experience excess sebum production which is associated with increased incidence of dermatological conditions such as acne or seborrheic dermatitis. Even in individuals without acne, excess sebum production detracts from the cosmetic appearance of the skin and hair by causing the skin to look shiny, greasy or oily and hair to look limp and dirty. Decreasing the production of sebum will alleviate oily skin and hair in individuals experiencing these conditions.
Current treatments for addressing the production of excess sebum are less than optimal. Isotretinoin, a non aromatic retinoid, has been shown to suppress sebum production by up to 90% but it is also associated with severe birth defects and a number of other potentially serious side effects. Thus, isotretinoin is only utilized for the treatment of severe acne and not simply for the reduction of sebum secretion for cosmetic purposes. Other aromatic retinoids, such as etretinate, are used in the treatment of acne but do not reduce sebum synthesis. Christos C. Zouboulis, J. Clin. Derm., 22: 360-366 (2004).
Consequently, the most practical means of alleviating excess sebum production is frequent washing of the skin's surface. While frequent washing removes excess sebum from the skin, this effect is temporary and does nothing to decrease sebum production. In fact, over-washing or washing with harsh products can dehydrate the skin and actually stimulate the sebaceous glands to increase, as opposed to decrease, sebum production.